Zingiber officinale belongs to the family Zingeberaceae, is cultivated in various parts of the world especially India, China, Mexico etc. It is a major spice crop cultivated in India and marketed as fresh and dried spice. It is perennial small grassy plant grown in all season through out the year. Indian ginger is famous for its flavor, texture and taste. More than spices, ginger is considered as tastemaker, drug, appetizer and flavourant. Ginger products are available in a variety of forms like oils, oleoresins, fresh ginger in brine, pickle, candies, syrup etc. Bleached and unbleached powder forms of ginger are also available in the market. India has a predominant position in ginger production and export. In the world market, Indian ginger is popularly known as Cochin ginger and Calicut ginger. The principal buyers are the Middle East, USA, UK and Netherlands. Ginger is commonly used for abdominal bloating, coughing, vomiting, diarrhea, rheumatism etc.
Ginger (Zingiber officinale) is cultivated mainly for its root part or rhizome. The proximate chemical composition of ginger has been investigated and has been shown to contain approximately 1-4% of volatile oils, which are the medically active constituents of ginger. The volatile oils consist of bisaboline, cineol, phelladrene, citral, borneal, citronellal, geramial, linalool, limonene, zingiberol, zingiberine, camphene etc. The oleoresin present in ginger is mainly gingerol and shogaol. The phenols detected in solvent extracts of ginger are mainly gingerol and zingerone. Zingibain a proteolytic enzyme is also present in ginger, in addition to other components such as vitamin B6, vitamin C, calcium, magnesium, phosphorus, potassium and linoleic acid etc. The pungency and aroma of ginger has been identified to be mainly due to gingerol, which contains alcohol group of the oleoresin, volatile oil respectively. This makes Ginger a free radical scavenger and its antimutagenic and anti-inflammatory properties, have been documented.
Gastric hyper acidity and ulcers are very common, causing human sufferings today. It is an imbalance between damaging factors within the lumen and protective mechanisms within the gastro duodenal mucosa. Prolonged anxiety, emotional stress, heamorrhagic surgical shock, burns and traumas are known to cause severe gastric irritation finally leading to ulcer and cancer. There are basically three causes for chronic peptic ulcer. One of the causes is hypersecretory status such as Zollinger-Ellisson syndrome where there is a high and uncontrolled production of acid leading to ulcer. Secondly the non steroidal anti-inflammatory drugs which are used for rheumatoid diseases also causes ulcer either as an aggressive factor causing lesions in the gastric mucosa or acting as inhibitor of protecting factors which renders the stomach defenseless to resist its own acid production. The third factor responsible for ulcer is a rod shaped pathogenic bacteria Helicobacter pylori, normally exists in human stomach. Upon harboring in the host, generates ammonia due to its strong urease activity thereby causes ulcers.
The concept of management of ulcer disease is fast changing. Treatment was based on the principle that excessive secretion of acid is the reason for ulcer symptoms. Gastric cells called parietal cells secreted the gastric acid. However understanding of the role of histamine, gastrin and acetylcholine in controlling gastric secretion lead to the designing of antiulcer drugs which act as blockers of such receptors. The role of enzymic gastric proton pump with proton potassium ATPase activity is very crucial in varieties of ulcers irrespective of the root cause. Therefore, blockers of proton potassium ATPase has been considered and explored to design antiulcer drugs such as omeprazole and Lansoprazole etc. However they cause lots of side effects especially in presence of non-steroidal inflammatory drugs, pregnancy, lactation and during alcoholic consumption etc. Current data provides an alternative source for the ulcer cure.
Ginger is used since time immemorial as a dietary component in daily life as a spicy material. Ayurvedic, Chinese and traditional medicine systems have recommended ginger as a medicinal plant. Ayurveda system considered ginger to be a truly wonder drug. Since exhibits analgesic, anti-emetic, aromatic, aphrodisiac, carminative, diaphoretic, digestive, expectorant, nervine, sialagogue and stimulant activity. It is also used against atherosclerosis, as chemotherapy support, against migraine headaches, morning sickness, motion sickness, nausea and vomiting followed by surgery, rheumatoid arthritis etc. Ginger is a classic tonic for the digestive tract. It stimulates digestion and keeps the intestinal muscles tuned. Ginger has been believed to protect the stomach from the damaging effect of alcohol and nonsteroidal anti-inflammatory drugs and this may help to prevent ulcers. In the present study antiulcer activity has been investigated in ginger extract. The potential antiulcer components have also been identified.
Reference may be made to the EP patent No. 0639379 of Feb. 11, 2003, where in, a procedure for the preparation of a ginger root infusion for desensitivity of teeth and gum to temperature changes. This preparation has been used undiluted as a mouthwash or as an additive to tooth paste, ointment, wax etc.
Reference may be made to JP patent No. 9087193 of Mar. 31, 1997 where in, an antihuman immunodeficiency virus agent effective for preventing the crisis of an healing acquired syndrome containing active ingredients in water extract of ginger family has been claimed.
Reference may be made to CN patent No. 390565 of Jan. 15, 2003 where in, a process for extracting the antibacterial active component from Zingiber officinale for treating inflammation and thrombocyte coagulation in a liquid form has been determined and this medical product has anti-inflammatory, antibacterial and anticoagulant activity.
Reference may be made to JP patent No. 2002047195 of Feb. 12, 2002 where in they claim the pharmaceutical composition containing active ingredient of ginger. They claimed that this preparation had anti-inflammatory, antiplatelet aggregation and antifungal activity.
Reference may be made to DE patent No. 19859499 of Jun. 29, 2000 where in, a stable ginger extract preparation has been shown to be useful for treating dyspepsia or travel sickness. This preparation contained oil, triglyceride or fatty acid or alcohol stabilizer.
Reference may be made to CN patent No. 1159343 of Sep. 17, 1997 where in, they claim a Chinese medicine preparation for curing stomachache and its composition is constituted by Chinese herbal medicine of aconite, dried ginger, licorice and chrysanthemum flower and has been claimed useful for treating oral cavity ulcers.
Reference may be made to U.S. Pat. No. 6,217,880 of Apr. 17, 2001 where in, a medicament has been developed for treating recurrent ulcer in mouth. and bechet's which was mainly prepared from root of coptis Chinesesis, isatis root, flower of lonicen rhemannia, Lilly bulb, bamboo leaf, coydalis bungeana, chinese wild ginger and ganoderma snake and thunder god vine in certain weight proportions. This medicament has the effect of clearing heat, diminishing inflammation, cooling blood and closing sores etc.
Reference may be made to CN patent No. 1334094 of Feb. 06, 2002 where in, an exterior applying medicine for treating cold and hot injury, bed sore and chronic ulcer has been claimed. The medicine constituted by brown sugar, pig bone oil, poppy cream, ginger juice and lidocaine powder through proportioning.
Reference may be made to CN patent No. 1337243 of Feb. 27, 2002 where in, a health care anticancer powder made up by using five natural plants, garlic, black pepper, paprika, tea and ginger was prepared. They claimed that this product could be made into products like anticancer tea, anticancer pills, anticancer powder, anticancer capsule, anticancer beer etc. This product was also used as plant pesticides, natural skin and hair protecting products as well as plant cosmetics.
Reference may be made to DE patent No. 102517523 of 15-05-2003 where in, they claim administration of ginger preferably as feed additive that can be used for the treatment of inflammation and or pain in horses.
Reference may be made to US patent No. 2004022875 of Feb. 05, 2004 where in, they claim a pharmaceutical composition comprising an effective amount of an extract of lyophilized extract or at least one bioactive fractions obtained from plant flower Woodfordia fruticosa along with one or more pharmaceutically acceptable additives or carriers for treating ulcer.
Reference may be made to WO patent No. 03080086 of 02-10-2003 where in, they claimed a novel synergistic herbal composition for the treatment of gastric ulcer. The herbal composition constituted by an aqueous extract Aegelemarmeles, Withania somnifra, Blechumorientale, Vitis vinifera, Feronia elephantanum, Punica granatum, 4-9% by wt of an extract from Zingiber officinale, Piper nigrum, Piper longum and Azadirachta indica along with one or more pharmaceutically acceptable additives or carriers.
Reference may be made to EP patent No. 1281402 of 05-02-2003, where in, they claim a novel method for the extraction of water soluble ginger root extract, which is different from the conventional one substantially free of gingerols serving as a stimulant or pungent ingredient and can be used as a material for cosmetics because of its hair growth inhibition and antipruritic actions.
Reference may be made to the article entitled “gastroprotective effect of Neem (Azadirechta indica) bark extract: possible involvement of H+ K+ ATPase inhibition and scavenging of hydroxyl radical” of Uday Bandyopadhyay et al. In Life sciences in (2002) vol. 71, p2845-2865 where they have reported the antisecretary and antiulcer effects of aqueous extract of Neem (Azadirachta indica) bark, and they also reported that the bark extract inhibits of H+ K+ ATPase in vitro in a concentration dependent manner.
Reference may be made to the article entitled “inhibition of gastric of H+ K+ ATPase and acid secretion by SCH 28080, substituted pyridyl(1,2a) imidazole” of Bjorn wallmark et al. In J B C in 1987 vol. 262, no. 5 p-2077-2084. Where they have reported a hydrophobic amine SCH 28080, 2, ethyl-8-(phenylmethoxy) imidazo(1,2a) pyridine-3-acetonotrile, inhibits gastric acid secretion in vivo and in vitro and their study on isolated H+ K+ ATPase showed that the compound inhibited the enzyme competitively with K+, whether ATP or p-nitrophenyl phosphate were used as substrates.
Reference may be made to the article entitled “Purification of an antiulcer polysaccharide from the leaves of Panax ginseng” of Sun X B et. al in Planta Med. in 1992 vol. 58, p-445-448 where they have reported that water soluble crude polysaccharide fraction from leaves and alkaline soluble crude polysaccharide from roots of this plant prevented HCl/ethanol induced ulcerogenesis in mice dose dependently. They have purified pectic polysaccharide of molecular weight mass 16 kDa and were composed of mainly galactose and galacturonic acid with small proportions of rhamnose, arabinose, mannose, glucose and glucuronic acid.
Reference may be made to the article entitled “Gastroprotective activity in ginger Zingiber officinale rose, in albino rats” of Al— Yahya M A et al in Am. J. Clin. Med in 1989 vol. 17 p 51-56 wherein they have showed the cytoprotective and gastroprotective effect of ginger in albino rats.
Reference may be made to the article entitled “The antiulcer effect in rats of ginger constituents” of Yamahara J et al in J. Ethanopharmacol in 1988 vol. 23 p 299-304 wherein they have determined the effects of ginger, a pungent stomachic natural medicine, on HCl/ethanol induced gastric lesions in rats.
Reference may be made to the article of Mahady G B et. al in Anticancer Res in 2003 vol. 5A p 3699-3702, where they have demonstrated that ginger root extracts containing the gingerols inhibit the growth of H.pylori Cag+ strains in vitro and chemopreventive effects.
Reference may be made to the article of Yoshikawa et.al in Chem Pharm Bull in 1994 vol. 42 p 1226-1230 wherein they have reported that 6-ginesulfonic acid showed more potent anti ulcer activity than 6-gingerol and 6-shogaol.
Reference may be made to the article of Thomson M et. al in Prostaglandins Leukot essent Fatty Acids in 2002 vol. 67 p 475-478 whereby they suggested that ginger could be a used as cholesterol-lowering, antithrombotic and anti-inflammatory agent.
Present invention reports a process for the preparation of antiulcer compounds from ginger (Zingiber officinale) rhizome. It indicates the presence of potent antiulcer polysaccharide as well as antioxidants. It is novel in that this is the first report on antiulcer polysaccharide from ginger from India and worldwide. The polysaccharide fraction and antioxidant fractions from ginger have been found to be very effective inhibitors of proton pump activity via H+ K+ ATPase inhibition (PPI) as well as inhibition of H. Pylori. The effective inhibitory concentration (ICe) of ginger polysaccharide and antioxidant is 27.2 and 16.5 μg GAE respectively.
The present invention is also novel in that                The effective H+ K+ ATPase (PPA) blockers are good antiulcer agents. The known PPA Inhibitors (PPI) poses lots of side effects such as dizziness; nausea, constipation and these drugs are not preferable during pregnancy and lactating mother.        The antiulcer compounds thus reported have the potency of inhibiting ulcer by multiroutes such as inhibition of acid secretion preferably by antioxidants, enhancement of mucosal defense by polysaccharide and inhibition of H. pylori and hence may be effective as antiulcer agent.        
The antioxidants present in the powder may also offer additional protectivity to the systems against oxidative stress such as lipid peroxidation, cytoprotection, DNA protection etc. polysaccharide thus found in the preparation may ensure the protection of mucin layer of parietal cell also.